Antibacterial and antifouling oxathiazines and their oxides

ABSTRACT

Use of 3-aryl-5,6-dihydro-1,4,2-oxathiazines and their oxides having the formula ##STR1## wherein n is 0, 1 or 2; R 1  is hydrogen, C 1-4  alkyl or benzyl; and R represents (a) phenyl; phenyl substituted with 1 to 3 substituents independently selected from hydroxyl, halo, C 1-12  alkyl, C 5-6  cycloalkyl, trihalomethyl, phenyl, C 1-5  alkoxy, C 1-5  alkylthio, tetrahydropyranyloxy, phenoxy, C 1-4  alkylcarbonyl, phenylcarbonyl, C 1-4  alkylsulfinyl, C 1-4  alkylsulfonyl, carboxy or its alkali metal salt, C 1-4  alkyloxycarbonyl, C 1-4  alkylaminocarbonyl, phenylaminocarbonyl, tolylaminocarbonyl, morpholinocarbonyl, amino, nitro, cyano, dioxolanyl or C 1-4  alkyloxyiminomethyl; naphthyl; pyridinyl; thienyl, preferably when n is not 2; furanyl; or thienyl or furanyl substituted with one to three substituents independently selected from C 1-4  alkyl, C 1-4  alkyloxy, C 1-4  alkylthio, halo, cyano, formyl, acetyl, benzoyl, nitro, C 1-4  alkyloxycarbonyl, phenyl, phenylaminocarbonyl and C 1-4  alkyloxyiminomethyl; or R represents a radical of formula ##STR2## wherein X is oxygen or sulfur, Y is nitrogen, CH or C(C 1-4  alkyloxy); and R&#34; is hydrogen or C 1-4  alkyl, as an antibacterial, anti-yeast, antifungal, algicidal, anticrustacean, molluscicidal and general antifouling agent and compositions containing the same.

This application is a division of U.S. patent application Ser. No.08/586,690, filed Jan. 25, 1996, now U.S. Pat. No. 5,712,275, which is a371 of PCT Application Ser. No. PCT/EP94/02784, filed Aug. 24, 1994,which is a Continuation-In-Part of U.S. patent application Ser. No.08/111,352, filed Aug. 24, 1993, now abandoned.

The present invention concerns a method of controlling bacteria andfouling organisms with 3-aryl-5,6-dihydro- 1,4,2-oxathiazines and theiroxides, a method of protecting non-living materials other than wood, andindustrial antibacterial and antifouling compositions. Surfaces ofobjects exposed to humid or aqueous environments are readily colonizedby microorganisms and occasionally by other, higher life forms such asmolluscs and crustacea. As these organisms settle on or attach to saidsurfaces, the value of the exposed objects diminishes. The exterior, butpossibly also the interior of the object may deteriorate, the surfacechanges (e.g. from smooth, clean and streamlined to rough, foul andturbulent), the weight of the object increases by the deposit of theorganisms and their remnants, and the vicinity of the object may becomeobstructed or encumbered. The function of the object and system involvedlowers and the quality of the aqueous environment deteriorates. Similarproblems beset industrially used compositions such as coatings,lubricants and the like. All these phenomena are refuted to as fouling.The oxathiazines of the present method and their oxides are disclosed inU.S. Pat. No. 4,569,690 as herbicides, plant fungicides, plantdesiccants and defoliants.

The present invention provides a method of controlling bacteria andfouling organisms, said method comprising applying to said bacteria orfouling organisms, or to the locus thereof an effective antibacterial orantifouling amount of a compound having the formula ##STR3## wherein nis 0, 1 or 2; R¹ is hydrogen, C₁₋₄ alkyl or benzyl; and R represents (a)phenyl; phenyl substituted with 1 to 3 substituents independentlyselected from hydroxyl, halo, C₁₋₁₂ alkyl, C₅₋₆ cycloalkyl,trihalomethyl, phenyl, C₁₋₅ alkoxy, C₁₋₅ alkylthio,tetrahydropyranyloxy, phenoxy, C₁₋₄ alkylcarbonyl, phenylcarbonyl, C₁₋₄alkylsulflnyl, C₁₋₄ alkylsulfonyl, carboxy or its alkali metal salt,C₁₋₄ alkyloxycarbonyl, C₁₋₄ alkylaminocarbonyl, phenylaminocarbonyl,tolylaminocarbonyl, morpholinocarbonyl, amino, nitro, cyano, dioxolanylor C₁₋₄ alkyloxyiminomethyl; naphthyl; pyridinyl; thienyl, preferablywhen n is not 2; furanyl; or thienyl or furanyl substituted with one tothree substituents independently selected from C₁₋₄ alkyl, C₁₋₄alkyloxy, C₁₋₄ alkylthio, halo, cyano, formyl, acetyl, benzoyl, nitro,C₁₋₄ alkyloxycarbonyl, phenyl, phenylaminocarbonyl and C₁₋₄alkyloxyiminomethyl; or R represents a radical of formula ##STR4##wherein X is oxygen or sulfur; Y is nitrogen, CH or C(C₁₋₄ alkyloxy);and R" is hydrogen or C₁₋₄ alkyl.

The present invention in particular provides a method of protectingnon-living materials other than wood, and the objects made of or coveredby said non-living materials, against bacteria and/or fouling organisms,said method comprising applying to the surface or incorporating intosaid materials or objects an effective antibacterial or antifoulingamount of a compound of formula (I).

In the foregoing definitions halo is generic to fluoro, chloro, bromoand iodo; C₁₋₄ alkyl defines straight and branch chained saturatedhydrocarbon radicals having from 1 to 4 carbon atoms comprising methyl,ethyl, n-propyl, 1-methylethyl, n-butyl, 1,1-dimethylethyl,1-methylpropyl, 2-methylpropyl; C₁₋₅ alkyl includes C₁₋₄ alkyl radicalsas defined above and saturated hydrocarbon radicals having five carbonatoms, e.g. n-pentyl and the branched pentyl isomers; C₁₋₆ alkylincludes C₁₋₅ alkyl radicals as defined above and six carbon containinghomologs, e.g. n-hexyl and the branched hexyl isomers. C₁₋₁₂ alkylincludes C₁₋₆ alkyl and saturated hydrocarbon radicals having from 7 to12 carbon atoms, e.g. heptyl, octyl, nonyl, decyl, undecyl and theirisomers. The term alkali metal cation in particular is a sodium orpotassium cation. Trihalomethyl defines a methyl group being fullysubstituted with halo atoms, in particular trifluoromethyl andtrichloromethyl. C₁₋₄ alkyloxyiminomethyl defines a radical of formula--CH═N--O--C₁₋₄ alkyl.

Particular compounds of formula (I) for use in the method are thosewherein n is 0, 1 or 2; R¹ is hydrogen, C₁₋₄ alkyl or benzyl; and Rrepresents phenyl; naphthyl; pyridinyl; thienyl provided that n is not2; furanyl optionally substituted with 1 to 3 substituents independentlyselected from C₁₋₄ alkyl and C₂₋₅ alkyloxycarbonyl; or phenylsubstituted with 1 or 2 substituents indepently selected from hydroxyl,halo, C₁₋₁₂ alkyl, C₅₋₆ cycloalkyl, trihalomethyl, phenyl, C₁₋₅ alkoxy,C₁₋₅ alkylthio, tetrahydropyranyloxy, phenoxy, C₂₋₅ alkylcarbonyl,phenylcarbonyl, C₁₋₄ alkylsulfinyl, C₁₋₄ alkylsulfonyl, carboxy or itsalkali metal salt, C₁₋₅ alkoxycarbonyl, C₂₋₅ alkylaminocarbonyl,phenylaminocarbonyl, tolylaminocarbonyl, morpholinocarbonyl, amino,nitro, cyano, or dioxolanyl.

Of interest are those compounds wherein n is 1 and R represents phenyl,thienyl or phenyl substituted with one or two substituents selected fromhalo and trihalomethyl; or those wherein n is 2 and R represents phenylor phenyl substituted with one or two substituents selected from haloand trihalomethyl.

Of further interest are the compounds wherein R¹ is hydrogen, n is 1 or2, and R represents phenyl, C₁₋₆ alkylphenyl, halophenyl, dihalophenyl,biphenyl, C₁₋₅ alkyloxyphenyl, trihalomethylphenyl, nitrophenyl, phenylsubstituted with C₂₋₅ alkyloxycarbonyl, C₁₋₆ alkylnitrophenyl,unsubstituted furanyl or thienyl, or furanyl or thienyl substituted withethoxycarbonyl, cyano, chlorine or bromine.

Of particular interest are the compounds wherein R¹ is hydrogen, n is 1or 2, and R represents 3-fluorophenyl, 4-chlorophenyl,3,4-dichlorophenyl, 3,5-dichlorophenyl, 3-trifluoromethylphenyl,4trifluoromethylphenyl, 4-methylphenyl, 3-ethanonephenyl, 3-nitrophenyl,3-methyl-4-nitrophenyl or 2-thienyl.

Also of further interest are those compounds of formula (I) wherein R¹is hydrogen, R is a radical of formula (b) wherein X is sulfur, Y isnitrogen or CH, and R" is hydrogen.

Preferred compounds are 5,6-dihydro-3-(2-thienyl)-1,4,2-oxathiazine,4-oxide and 3-(4-chlorophenyl)-5,6dihydro-1,4,2-oxathiazine, 4,4dioxide.

All compounds of formula (I) can be prepared following the proceduresdescribed in U.S. Pat. No. 4,569,690.

The compounds of formula (1) are active against gram-positive bacteriaand, more importantly for use in material protection, also againstgram-negative bacteria Susceptible bacteria belong to genera such asAeromonas, Alcaligenes, Brevibacterium, Cellulomonas, Citrobacter,Corynebacterium, Enterobacter, Escherichia, Klebsiella, Micrococcus,Proteus, Providencia, Pseudomonas, Shewanella, Acinobacter, Bacillus,Serratia, Staphylococcus, Streptococcus and Xanthomonas.

The compounds of formula (I) further are active against foulingorganisms. The term "fouling organisms" is meant to comprise organismsthat grow on or adhere to various kinds of surfaces, in particular inhumid or aqueous environments such as, marine waters, fresh waters,brackish waters, rain water, and also cooling water, drainage water,waste water and sewage. Fouling organisms are Algae such as, forexample, Microalgae, e.g. Amphora, Achnanthes, Navicula, Amphipora,Melosira, Cocconeis, Chlamydomonas, Chlorella, Ulothrix, Anabaena,Phaeodactylum, Porphyridium; Macroalgae, e.g. Enteromorpha, Cladophora,Ectocarpus, Acrochaetium, Ceramium, Polysiphonia; Molluscs, e.g.Mytilus, Crustacea, e.g. Artemia, Balanus, Elminius Modestus, Verruca,Lepas and Ascidia, Hydrozoa and Bryozoa.

The present invention also provides a method for the preservation ofnon-living materials other than wood against fungi that spoil or destroysuch materials. Said method involves treating such materials with aneffective fungicidal amount of a compound of formula (I).

The compounds of formula (I) are useful to protect a wide variety ofnon-living materials other than wood, and the objects made thereof orcovered thereby. Examples of non-living materials and the objects madethereof or covered thereby comprise adhesives; sizes; paper andcardboard, pulp; textiles; leather, paints; plastics, e.g. PVC andpolyester; industrial compositions such as cooling media, e.g. coolinglubricants and cutting fluids, coating compositions, bath compositions(process liquids), lubricants and the like; metals and alloys such asiron and steel; building materials, e.g. bricks, (paving) stones, cementand concrete; decorating materials, e.g. plaster, tiles; and any othermaterials that can be contaminated or destroyed by bacteria, fungi orfouling organisms.

Of particular interest are coating materials conventionally employed fordecorative and protective purposes. The present method is especiallysuited for protecting adherent coatings, whether clear or colored (i.e.comprising one or more dyes or pigments), and whether natural orsynthetic, such as, for example, paints--especially antifouling paintcompositions--, varnishes, lacquers, finishes, whitewash and similarcoatings. The particular aptness of the present method of protectingsaid coating materials resides in the fact that the oxathiazinesemployed in the method not only effectively protect the coating materialin storage containers, during "in can" conservation (especially againstbacteria) thus ensuring a long pot (or can) life and good storagestability, but also effectively protect the coating material andoptionally its underlying substrate when it has been applied as a filmto said substrate ("film" conservation). The simultaneous utility of theoxathiazines for both "in can" and "film" conservation of coatings is ofgreat practical value.

As constructions made of or covered by said non-living materials therecan be mentioned swimming pools, baths, cooling water circulationcircuits and industrial baths in various installations, e.g. inmanufacturing plants or in air-conditioning installations, the functionof which can be impaired by the presence and/or the multiplication ofbacteria and fouling organisms. Further examples are buildings and partsof buildings such as floors, outer and inner walls or ceilings, ofplaces suffering from dampness such as cellars, bathrooms, kitchens,washing houses and the like, and which are hot-beds for bacteria and/orfouling organisms. The presence of these organisms not only isproblematic from the viewpoint of hygiene and aesthetics, but alsocauses economic losses because said buildings and/or decoratingmaterials deteriorate more rapidly than desired.

The method is especially suitable to protect underwater objects such as,for example, shiphulls, harbour installations, drying docks,sluice-gates, locks, mooring masts, buoys, drilling platforms, bridges,pipelines, fishing nets, cables and any other object in constant orfrequent contact with water, by applying to said objects an antifoulingcomposition, e.g. paint composition, comprising an effective antifoulingamount of a compound of formula (I).

In this context it should be noted that the present method provides asafer and ecologically more acceptable alternative for current methodsusing antifouling products based on heavy metals such as cuprous oxideand the like, or those based on organometallic derivatives such asorgano-tin compounds. The toxicity of the oxathiazines to mammals isacceptable and as such they are less hazardous for humans whether thesecompounds reach the human body by direct physical contact (e.g. duringhandling or application) or via the food chain. Their biodegradabilityensures that they are less persistent in the environment and that theycause less and shorter environmental pollution and stress. The chemicalstability of the oxathiazines furthermore implies that they arecompatible with most non-living materials as such and do need specialprecautions such as the addition of agents for stabilizing the activeingredient. In materials that should form films such as lubricants,cutting fluids and coating materials, they do not impair the formationof uniform films and the practicability. In particular, in coatingmaterials they do not impair rapid curing in practical circumstancessuch as room temperature and outdoor conditions, and allow for strongadhesion of the composition to the substrate and/or the topcoat.

The method of application is chosen in accordance with the intendedobjective and the prevailing circumstances. For instance, the techniqueused in the case of protecting lubricants, coatings or cutting fluidscomprises mixing the active ingredient in said lubricants, coatings orfluids either during the manufacturing process or alternativelyafterwards in the finished product. The active ingredient can be addedin neat form or dissolved or suspended in a sufficient amount ofdiluent. Preferably the diluent consists of one or more of the solventsas they occur in the final composition.

The method also comprises applying compounds of formula (I), optionallyin an appropriate formulation, to non-living materials by any of thetechniques known in the art such as, for example, brushing, spraying,atomising, dipping, soaking, immersing, scattering and pouring. In someinstances, the application may involve impregnation techniques usingpressure or vacuum systems, thermal systems, injection or diffusion.

Appropriate formulations are formulated following art-known proceduresto emulsifiable concentrates, directly sprayable or dilutable solutions,dilute emulsions, wettable powders, soluble powders, pastes, dusts,granulates, coating compositions, e.g. paints--in particular antifoulingpaint compositions--, lacquers and the like. For example, the activecompound can be mixed with an extender, which consists of a liquid,semi-solid or solid carrier, and optionally surface-active agents suchas emulsifiers and/or dispersing agents. In coating compositions, theactive compound may advantageously be incorporated in polymers,copolymers or resins. These can consist of such monomers as dialkyl(dimethyl) siloxanes, (meth)acrylic acid, (meth)acrylic acid esters,vinyl and allyl alcohols and derived esters (e.g. vinyl acetate), maleicacid, styrene, vinylchloride, butadiene, acrylamide, acrylonitrile andthe like copolymerizable monomers. As resins there may be mentionedalkyd resins, polyurethanes, epoxy resins, phenolic resins andurea-formaldehyde resins. Further useful additives in said compositionscomprise water-repelling agents and surface slipping agents that arecapable of imparting a low surface tension of the coating film formed bythe polymer or copolymer in the coating compositions.

Any suitable carrier or additive that does not interfere with theantibacterial nor the antifouling activity of the active ingredient canbe used in the compositions of the present invention. The solid carriersor fillers used e.g. for dusts and powders include various inert, porousand pulverous distributing agents of inorganic or organic nature suchas, for example, the natural mineral fillers, e.g. calcite, talcum,kaolin, montmorillonite or attapulgite, or fillers of organic nature,e.g. powdered cork, sawdust and other fine pulverous materials. In orderto improve their physical properties it can be advantageous to addhighly dispersed silicic acid or highly dispersed absorbent polymers.Suitable granulated absorbent carriers are of the porous type, forexample, pumice, broken brick, sepiolite or bentonite; and suitablenonsorbent carriers are materials such as calcite or sand. The activeingredient is mixed with these carrier substances, for example, by beingground therewith; alternatively, the inert carrier substance isimpregnated with a solution of the active component in a readilyvolatile solvent and the solvent is thereafter removed by heating or byfiltering with suction at reduced pressure. By adding wetting and/ordispersing agents, such pulverous preparations can also be made readilywettable with water, so that suspensions are obtained upon dilution.

Inert diluents used for the production of liquid preparations shouldpreferably not be readily inflammable and should be as far as possiblenon-toxic to nontarget animals or plants and humans in the relevantsurrounding. Diluents suitable for this purpose are, for example, wateror, organic solvents such as, for example, aromatic hydrocarbons, e.g.methylbenzene, dimethylbenzene mixtures, substituted naphthalenes;alcohols and glycols and their ethers and esters, e.g. ethanol, ethyleneglycol, ethylene glycol monomethyl or monoethyl ether; ketones e.g.2-propanone, cyclohexanone and the like; strongly polar solvents; e.g.N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide;vegetable oils or epoxidized vegetable oils such as epoxidized coconutoil or soybean oil, and mixtures thereof. Solutions can be prepared inthe usual way, if necessary, with assistance of solution promoters.Other liquid forms which can be used consist of emulsions, dispersionsor suspensions of the active compound in water or suitable inertdiluents, or also concentrates for preparing such emulsions, dispersionsor suspensions which can be directly adjusted to the requiredconcentration. For this purpose, the active ingredient is, for example,mixed with a dispersing, suspending or emulsifying agent. The activecomponent can also be dissolved or dispersed in a suitable inert solventand mixed simultaneously or subsequently with a dispersing oremulsifying agent. It is also possible to use semi-solid carriersubstances of cream, ointment, paste or waxlike nature, into which theactive ingredient can be incorporated, if necessary, with the aid ofsolution promoters and/or emulsifiers. Vaseline, petroleum wax, liquidparaffin, silicone oil and other cream-bases are examples of semi-solidcarrier substances. Furthermore, it is possible for the activeingredient to be used in the form of aerosols. For this purpose theactive ingredient is dissolved or dispersed in a volatile liquidsuitable for use as a propellant, for example, chlorinated and/orfluorinated derivatives of methane and ethane and mixtures thereof, orcompressed air. In this way solutions under pressure are obtained which,when sprayed, yield aerosols that are particularly suitable forcontrolling or combatting bacteria and/or fouling organisms, e.g. inclosed chambers and storage rooms. For the latter purpose also smokegenerators containing the active ingredient can be used.

Besides the compounds of formula (I) and the carrier, appropriateformulations often comprise other adjuvants conventionally employed inthe art of formulation. These depend on specific applications and theuser's preference. Such adjuvants are, for example, organic bindingagents (e.g. chemically drying organic binder-forming polymers such asalkyd resins or physically drying organic binder-forming solids bysolvent evaporation); insecticides such as, for example, chlorinatedhydrocarbons, e.g. endosulfan, organophosphates, e.g. chloropyriphos,pyrethroids, e.g. permethrin and the like; additional fungicides andbactericides such as alcohols, e.g. ethanol, 2,3,3-triiodallyl alcohol;aldehydes, e.g. formaldehyde, glutaraldehyde; formaldehyde releasingcompounds, e.g. 2-bromo-2-nitro-propane-1,3-diol (bronopol),2-bromo-2-nitropropan-1-ol; reaction products of amines andformaldehyde, e.g. triazines,3,5-dimethyltetrahydro-1,3,5-2H-thiadiazine-2-thione; reaction productsof amides and formaldehyde, e.g.1-hydroxymethyl-2-thiono-1,2-dihydro-benzothiazol-N-hydroxymethylbenzothiazolinthione;phenols, e.g. 2-phenylphenol, pentachlorophenol; organic acids, e.g.propionic acid, benzoic acid, salicylic acid, naphthenic acid coppersalts; inorganic acids, e.g. boric acid; amides, e.g.2,5-dimethyl-N-cyclohexyl-N-methoxy-furan-3-carbonamide; carbamates,e.g. 3-iodopropargyl-N-butylcarbamate (IPBC),methyl-N-benzimidazol-2-ylcarbamate (Carbendazim),methyl-N-(1-butylcarbamoyl)benzimidazol-2-ylcarbamate (benomyl), zincdimethyldithiocarbamate, zinc ethylenebisdithiocarbamate,bis-(dimethylthiocarbamoyl)disulphide; pyridine derivatives, e.g.2-mercapto-pyridine-N-oxide, 2-chloro-6-(trichloromethyl)pyridine,2,3,5,6-tetrachloro-4-(methylsulphonyl)pyridine, copper8-hydroxyquinoline,1-ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid;azoles, e.g. tebuconazole, propiconazole, azaconazole, imazalil;heterocyclic compounds, e.g. 2-methyl-3(2H)-isothiazolone,5-chloro-2-methyl-3(2H)-isothiazolone, 2-n-octyl-4-isothiazolin-3-one,4,5-dichloro-2-(n-octyl)-4-isothiazolin-3-one,1,2-benzisothiazolin-3-one,2-methyl-4,5-trimethylene-4-isothiazolin-3-one,2-(4-thiazolyl)-benzimidazole, 2-mercaptobenzothiazole,2-(thiocyanomethylthio)benzthiazole; N-haloalkylthio compounds, e.g.N-trichloromethylthiophthalimide, folpet,N-trichloromethylthio-4-cyclohexane-1,2-dicarboximide, captan,N-1,1,2,2-tetrachloroethylthio-4cyclohexene-1,2-dicarboximide, captafol,dichlofluanide, tolylfluanide; compounds with activated halogen groups,e.g. chlorothalonil; surface active agents, e.g. guanidines andbiguanides; organometallic compounds, e.g. bis(tri-n-butyltin-oxide,tributyltin esters, tributyltin naphthenate, tributyltin linoleate,tributyltin benzoate, tributyltin fluoride; various compounds, e.g.pimaricine, tridemorph, methylene bisthiocyanate, tolyl sulfone,dicyanobutane; metal salts, e.g. chrome-copper-arsenic; active naturalproducts, e.g. streptomycin; auxiliary solvents such as ethylglycolacetate and methoxypropylacetate; processing additives; fixatives suchas carboxymethyl-cellulose, polyvinyl alcohol, paraffin; plasticizerssuch as benzoic acid esters and phthalates, e.g. dibutyl phthalate,dioctyl phthalate, didodecyl phthalate; UV-stabilizers or stabilityenhancers; dyes; color pigments; siccatives such as cobalt octoate, leadoctoate and cobalt naphthenate; corrosion inhibitors; antisettlingagents; anti-skinning agents such as methyl ethyl ketoxime; antifoamingagents and the like. Generally, the adjuvants are not essential to thepractice of the present invention but are included in particularformulations, especially in coating formulations to optimize overalleffectiveness and ease of application. They can be used therein in theconventional amounts.

The antibacterial and/or antifouling compositions which are employed inthe method of the invention can contain from 0.001% to 95% of the activeingredient by weight based on the total weight of the composition.Ready-to-use compositions such as paints preferably contain from 0.5% to20%, in particular from 1 to 10% by weight of the active ingredient.Antifouling paint compositions on the other hand can contain from 10 upto 75%, in particular from 20 to 70% of the active ingredient of formula(I) by weight based on the total weight of the dry mass of saidcomposition (i.e. up to 50%, in particular from 5 to 25% of the activeingredient by weight based on the total weight of the antifoulingcomposition). Preferred compositions are composed in particular of thefollowing constituents (all percentages are by weight):

Emulsifiable concentrates

active ingredient: 1 to 20%, preferably 5 to 10%

surfactant: 5 to 30%, preferably 10 to 20%

liquid carrier: 50 to 94%, preferably 70 to 85%

Dusts

active ingredient: 0.1 to 10%, preferably 0.1 to 1%

solid carrier: 99.9 to 90%, preferably 99.9 to 99%

Suspension concentrates

active ingredient: 5 to 75%, preferably 10 to 50%

water: 94 to 25%, preferably 88 to 30%

surfactant: 1 to 40%, preferably 2 to 30%

Granulates

active ingredient: 0.5 to 30%, preferably 3 to 15 %

solid carrier: 99.5 to 70%, preferably 97 to 85%

The following examples are not intended to limit, but to illustrate thescope of the invention.

A. BIOLOGICAL EXAMPLES Example 1 Efficacy against Bacteria and Yeasts

Test solutions were prepared by dissolving the compounds shown in Tables1-4 in 50% ethanol and further diluting with sterile distilled water.These test solutions were pipetted into Petri dishes and mixed with warmtryptose agar to reach an active ingredient concentration of 100 ppm.After cooling, the medium was inoculated with the following yeasts orbacteria:

Debaryomyces hansenii (yeast) (A)

Pseudomonas alcaligenes (gram neg) (B)

Bacillus cereus mycoides (gram pos) (C)

Pseudomonas aeruginosa (gram neg) (D)

Flavobacterium sp. (gram neg) (E)

Strepromyces albus (gram pos) (F)

Enterobacter aerogenes (gram neg) (G)

Escherichia coli (gram neg) (H)

After sufficient growth of the untreated cultures, the compounds wereevaluated using the following rating system:

0=growth equal to control.

1=inhibition of growth by the compound.

2=no growth under the influence of the compound.

The scores measured for antibacterial and antifouling efficacy of thecompounds of this invention are listed in Tables 1-4. The sign `-`signifies the compound was not tested

                  TABLE 1    ______________________________________    1 #STR5##    Compounds        Bacteria    Co. no.          n     R            A   B   C   D   E   F   G   H    ______________________________________     1    1     4-chlorophenyl                             2   1   2   0   2   2   0   2     2    2     2,4-dichlorophenyl                             2   0   2   0   2   0   0   0     3    1     3-nitrophenyl                             2   2   2   1   2   2   1   2     4    1     3,4-dichlorophenyl                             2   1   2   0   2   2   0   2     5    2     2-methylphenyl                             2   0   2   0   2   2   0   1     6    1     3-fluorophenyl                             2   1   2   0   2   2   0   2     7    1     2-furanyl    2   1   2   0   2   0   0   0     8    1     2-thienyl    2   2   2   1   2   2   2   2     9    1     3-methoxyphenyl                             0   0   0   0   0   0   0   0    10    1     4-methylphenyl                             2   1   2   1   2   2   0   2    11    2     4-methylphenyl                             2   1   1   1   2   1   0   0    12    2     2-furanyl    0   0   0   0   0   0   0   0    13    1     3-trifluoromethyl                             2   0   2   0   2   2   0   2                phenyl    14    1     4-ethanonephenyl                             2   1   2   1   2   2   0   2    15    1     2,6-dichlorophenyl                             1   0   1   0   0   0   0   0    16    2     2,6-dichlorophenyl                             2   0   2   0   0   0   0   0    17    2     phenyl       0   0   0   0   0   0   0   0    18    2     4-chlorophenyl                             --  1   2   0   2   2   0   0    19    2     3,5-dichlorophenyl                             --  0   2   0   2   2   0   0    20    1     4-butoxyphenyl                             0   0   0   0   0   0   0   0    21    1     3,5-dichlorophenyl                             --  2   2   0   2   2   0   0    22    1     4-benzoic acid                             --  1   0   0   2   2   0   0                ethyl ester    23    2     3-chlorophenyl                             0   0   0   0   0   0   0   0    24    2     4-trifluoromethyl                             --  0   2   0   2   2   2   0                phenyl    25    1     4-trifluoromethyl                             --  1   2   0   2   2   0   0                phenyl    26    1     3-benzoic acid,                             --  0   2   0   2   2   0   0                methyl ester    27    2     3-bromophenyl                             --  1   2   0   2   2   0   2    28    1     4-ethoxyphenyl                             --  0   0   0   2   2   0   0    ______________________________________

                  TABLE 2    ______________________________________    2 #STR6##    Co.                                         M.P.    No.  R.sup.1                R.sup.2                       R.sup.3 R.sup.4  X   n   (° C.)    ______________________________________    29   H      H      H       CO.sub.2 CH.sub.3                                        O   0   85-89    30   H      H      H       CO.sub.2 CH.sub.3                                        O   2   126-129    31   H      H      H       CO.sub.2 CH.sub.3                                        O   1   118-119    32   H      CH.sub.3                       H       H        S   0   oil    33   H      CH.sub.3                       H       H        S   1   73-75    34   H      H      H       H        S   2    99-101    35   H      H      H       Br       S   0   82-83    36   H      H      H       Br       S   1   113-114    37   H      CH.sub.3                       H       H        S   2   60-62    38   H      H      H       Br       S   2   118-119    39   H      H      CO.sub.2 CH.sub.3                               CH.sub.3 O   0   87-88    40   H      H      Br      H        S   0   74-75    41   H      H      Br      H        S   1   169-173    42   H      H      Br      H        S   2   126-127    43   H      H      CO.sub.2 CH.sub.3                               CH.sub.3 O   2   156-157    44   H      H      CO.sub.2 CH.sub.3                               CH.sub.3 O   1   147-148    45   H      H      CH.sub.3                               CO.sub.2 CH.sub.3                                        S   1   150-152    46   H      H      CH.sub.3                               CO.sub.2 CH.sub.3                                        S   2   125-126    47   H      H      H       CH.sub.3 S   0   62-63    48   H      H      H       CH.sub.3 S   1   109-111    49   H      H      H       CH.sub.3 S   2   101-102    50   CH.sub.3                H      H       H        S   1   114-115    51   CH.sub.3                H      H       H        S   2   147-148    52   CH.sub.3                H      H       H        S   0   70-72    53   H      H      H       CO.sub.2 CH.sub.2 CH.sub.3                                        S   0   68-69    54   H      H      H       CO.sub.2 CH.sub.2 CH.sub.3                                        S   1   109-110    55   H      H      H       CO.sub.2 CH.sub.2 CH.sub.3                                        S   2   123-124    56   H      H      H       CN       S   0   136-137    57   H      H      H       CN       S   1   160-162    58   H      H      H       CN       S   2   153-155    59   H      H      H       Cl       S   0   74-77    60   H      H      H       Cl       S   1   102    61   H      H      H       Cl       S   2   113-114    62   H      H      H       CHO      S   0   48-49    63   H      H      H       NO.sub.2 S   0   162-163    64   H      H      H       NO.sub.2 S   1   186-188    65   H      H      H       NO.sub.2 S   2   160-161    66   H      H      H       CH═NOCH.sub.3                                        S   2   168-170    67   H      H      H       C.sub.6 H.sub.5                                        S   0   100-103    68   H      H      H       C.sub.6 H.sub.5                                        S   1   144-147    69   H      H      H       C.sub.6 H.sub.5                                        S   2   95-98    70   H      H      NO.sub.2                               C.sub.6 H.sub.5                                        S   0   140-145    71   H      H      CH.sub.3                               Br       S   0   oil    72   H      H      CH.sub.3                               Br       S   1   100-104    73   H      H      Br      CH.sub.3 S   0   64-67    74   H      H      COOH    CH.sub.3 O   0    75   H      H      CONHC.sub.6 H.sub.5                               CH.sub.3 O   0    76   H      H      CONHC.sub.6 H.sub.5                               CH.sub.3 O   0    77   H      H      CONHC.sub.6 H.sub.5                               CH.sub.3 O   0    ______________________________________

                  TABLE 2a    ______________________________________    3 #STR7##    Co. No.   R.sup.2      n     M.P. (° C.)    ______________________________________    78        H            2     102-104    79        H            1     106-107    ______________________________________

                  TABLE 3    ______________________________________    4 #STR8##    Co. No. R"     X       Y          n   M.P. (° C.)    ______________________________________    80      H      O       N          2   255    81      H      O       N          1   190-191    82      H      O       N          0   143-144    83      H      S       N          2   226-227    84      H      S       N          0   150-151    85      H      S       N          1   192-195    86      H      S       CH         0   132-134    87      H      S       CH         1   140-142    88      H      S       CH         2   150-154    89      CH.sub.3                   O       N          1   209-210    90      CH.sub.3                   O       N          2   215-216    91      H      S       C--OCH(CH.sub.3).sub.2                                      1   oil    ______________________________________

                  TABLE 4    ______________________________________    5 #STR9##    Co. No.          R.sup.8     R.sup.9    R.sup.10                                       n   M.P. (° C.)    ______________________________________    92    H           F          H     2   136-138    93    H           F          H     1   132-133    94    F           F          H     2   106-108    95    F           F          H     1   128-130    96    F           F          H     0   63-65    97    CF.sub.3    H          CF.sub.3                                       1   110-113    98    CF.sub.3    H          CF.sub.3                                       0   44-48    99    CF.sub.3    H          CF.sub.3                                       2   76-78    100   F           H          F     0   103-104    101   F           H          F     2   108-110    102   F           H          F     1   138-139    103   CO.sub.2 CH(CH.sub.3).sub.2                      Cl         H     0   oil    104   CO.sub.2 CH(CH.sub.3).sub.2                      Cl         H     1   127-129    105   CO.sub.2 CH(CH.sub.3).sub.2                      Cl         H     2   82-83    106   H           CH═NOCH.sub.3                                 H     1   85-87    107   H           CH═NOCH.sub.3                                 H     2   104-106    ______________________________________

Example 2 Efficacy against Fresh-water Algae

9 of Bold's algal broth containing an appropriate concentration of testcompound, was inoculated in a 5.5 cm diameter plastic Petri dish with 1ml of a two week old stock culture of one of three species of greenalgae (Chlamydomonas dysosmos, Chlorella vulgaris or Ulothrixconfervicola) or the blue-green bacterium Anabaena cylindica. The disheswere incubated in a climate room under a photosynthetically activeradiation level of 40 μmole.m⁻².sec⁻¹ at 20° C. during the day (16 h)and 18° C. at night (8 h). Evaluation was performed after 14 days byvisually estimating the percentage of algal growth as compared tocontrols. Results are expressed as minimum test concentration (in ppm)giving 90% mortality.

    ______________________________________              Concentration (ppm)    Compounds   Chlamy-    Co.                 domonas                               Chlorella                                      Ulothrix                                              Anabaena    no.  n     R        dysosmos                               vulgaris                                      confervicola                                              cylindrica    ______________________________________     4   1     3,4-     2.5    10     2.5     2.5               dichloro-               phenyl     8   1     2-thienyl                        2.5     5     1       2.5    18   2     4-chloro-                        2.5    10     5       2.5               phenyl    19   2     3,5-     5      10     2.5     2.5               dichloro-               phenyl    21   1     3,5-     1       5     1       2.5               dichloro-               phenyl    25   1     4-       2.5    10     2.5     5               trifluoro-               methyl               phenyl    ______________________________________

Example 3 Efficacy against Marine Algae

9 ml of Provasoli ASP-2 (Artificial Seawater-2) medium containing anappropriate concentration of test compound, was inoculated in a 5.5 cmdiameter plastic Petri dish with 1 ml of a two weeks old stock cultureof the diatom Phaeodactylum tricornutum or the unicellar red algaPorphyridium sp. The dishes were incubated in a climate room under aphotosynthetically active radiation level of 40 μmole.m⁻².sec⁻¹ at 20°C. during the day (16 h) and 18° C. at night (8 h). Evaluation wasperformed after 14 days by visually estimating the percentage of algalgrowth as compared to controls. Compounds 1, 2, 3, 4, 5, 14, 15, 16, 18,19, 21, 25, 27 caused 90% mortality at concentration levels equal to orlower than 1 ppm.

Example 4 Efficacy against Artemia

Into 1 ml of artificial sea-water containing different amounts of thetest compound, approximately 15 Artemia Instar II larvae were added.After 24 hours of static incubation with continuous illumination thetest was evaluated.

Compounds 2, 4, 5, 11, 13, 18, 19 caused 100% mortality at concentrationlevels equal to or lower than 10 ppm.

B. COMPOSITION EXAMPLES

(all percentages are by weight)

Example 5

Composition examples for solid compounds of formula (I)

a) Emulsifiable concentrates: emulsions of any concentration could beobtained from these concentrates by dilution with water.

    ______________________________________                         a)   b)    ______________________________________    compound of formula (I)                           10%    1%    octylphenol polyethylene glycol ether                            3%    3%    (4-5 moles of ethylene oxide)    calcium dodecylbenzenesulfonate                            3%    3%    castor oil polyglycol ether                            4%    4%    (36 moles of ethylene oxide)    cyclohexanone          30%    10%    dimethylbenzene mixture                           50%    79%    ______________________________________

b) Dusts: were obtained by mixing the active ingredient with thecarriers, and grinding

    ______________________________________                      a)    b)    ______________________________________    compound of formula (I)                         0.1%    1%    talcum              99.9%   --    kaolin              --      99%    ______________________________________

c) Suspension concentrates from which suspensions of any desiredconcentration could be obtained by dilution with water were obtained byintimately mixing finely ground

    ______________________________________                         a)   b)    ______________________________________    compound of formula (I)                           40%    5%    ethylene glycol        10%    10%    nonylphenol polyethylene glycol ether                            6%    1%    (15 moles of ethylene oxide)    sodium lignosulfate    10%    5%    carboxymethylcellulose  1%    1%    37% aqueous formaldehyde solution                           0.2%   0.2%    silicone oil in the form of a 75%                           0.8%   0.8%    aqueous emulsion    water                  32%    77%    ______________________________________

Example 6

Composition examples for liquid active ingredients of formula (I)

a) Emulsifiable concentrates: emulsions of any concentration could beobtained from these concentrates by dilution with water.

    ______________________________________                        a)   b)       c)    ______________________________________    compound of formula (I)                          20%    40%      50%    calcium dodecylbenzenesulfonate                           5%     8%      5.8%    castor oil polyethylene glycol ether                           5%    --       --    (36 moles of ethylene oxide)    tributylphenol polyethylene glycol ether                          --     12%      4.2%    (30 moles of ethylene oxide)    cyclohexanone         --     15%      20%    dimethylbenzene mixture                          70%    25%      20%    ______________________________________

b) Solutions suitable for application in the form of microdrops.

    ______________________________________                   a)    b)      c)      d)    ______________________________________    compounds of formula (I)                     80%     10%      5%   95%    ethylene glycol monoethyl ether                     20%     --      --    --    polyethylene glycol (MG 400)                     --      70%     --    --    N-methyl-2-pyrrolidone                     --      20%     --    --    epoxidised coconut oil                     --      --       1%    5%    petroleum distillate (boiling range                     --      --      94%   --    160-190° C.)    ______________________________________

c) Granulates: prepared by dissolving the active ingredient indichloromethane, spraying the solution onto the carrier, andsubsequently evaporating the solvent.

    ______________________________________                       a)   b)    ______________________________________    compound of formula (I)                          5%    10%    kaolin               94%    --    highly dispersed silicic acid                          1%    --    attapulgite          --     90%    ______________________________________

d) Dusts: were obtained by intimately mixing the carriers with theactive ingredient.

    ______________________________________                       a)   b)    ______________________________________    compound of formula (I)                          2%     5%    highly dispersed silicic acid                          1%     5%    talcum               97%    --    kaolin               --     90%    ______________________________________

Example 7

Composition examples for paints

    ______________________________________    a)     Compound of formula (I)  6.0%           Titanium dioxide         17.1%           Whiting                  9.7%           Talc                     13.2%           Calgon                   0.1%           Hydroxyethylcellulose (3% solution in water)                                    12.5%           Co-solvent               1.2%           Minor additives          0.4%           Water                    27.7%           Vinyl acetate/verstate copolymer emulsion                                    12.1%    b)     Compound of formula (I)  1.0%           Titanium dioxide         26.4%           Soya alkyd resin         44.0%           White spirit             27.5%           Cobalt octoate (8%)      0.3%           Lead octoate (33%)       0.7%           Methyl ethyl ketoxime    0.1%    ______________________________________

I claim:
 1. A coating composition in the form of a paint, varnish,lacquer or whitewash comprising:a) as active ingredient an effectiveantibacterial or antifouling amount of a compound of formula I ##STR10##wherein n is 0, 1 or 2; R is hydrogen, C₁₋₄ alkyl or benzyl; and Rrepresents phenyl; phenyl substituted with 1 to 3 substituentsindependently selected from hydroxyl, halo, C₁₋₁₂ alkyl, C₅₋₆cycloalkyl, trihalomethyl, phenyl, C₁₋₅ alkoxy, C₁₋₅ alkylthio,tetrahydropyranylox, phenoxy, C₁₋₄ alkylcarbonyl, phenylcarbonyl, C₁₋₄alkylsulfinyl, C₁₋₄ alkylsulfonyl, carboxy or its alkali metal salt,C₁₋₄ alkyloxycarbonyl, C₁₋₄ alkylaminocarbonyl, phenylaminocarbonyl,tolylaminocarbonyl, morpholinocarbonyl, amino, nitro, cyano, dioxolanylor C₁₋₄ alkyloxyiminomethyl; naphthyl; pyridinyl, thienyl; furanyl; orthienyl or furanyl substituted with one to three substituentsindependently selected from C₁₋₄ alkyl, C₁₋₄ alkyloxy, C₁₋₄ alkylthio,halo, cyano, formyl, acetyl, benzoyl, nitro, C₁₋₄ alkyloxycarbonyl,phenyl, phenylaminocarbonyl and C₁₋₄ alkyloxyiminomethyl; or Rrepresents a radical of formula (II) ##STR11## wherein X is oxygen orsulfur; Y is nitrogen, CH or C(C₁₋₄ alkyloxy); and R" is hydrogen orC₁₋₄ alkyl, and (b) polymers or copolymers derived from monomersselected from the group consisting of dialkyl siloxanes, (meth)acrylicacid, (meth)acrylic acid esters, vinyl and allyl alcohols and derivedesters, maleic acid, styrene, vinylchloride, butadiene, acrylamide,acrylonitrile, and resins selected from the group consisting of alkydresins, polyurethanes, epoxy resins, phenolic resins andureaformaldehyde resins.
 2. A coating composition according to claim 1further comprising one or more additives selected from the groupconsisting of water-repelling agents; surface slipping agents; organicbinding agents; insecticides; fungicides; bactericides; auxiliarysolvents; processing additives; fixatives; plasticizers; UV-stabilizersor stability enhancers; dyes; color pigments; siccatives; corrosioninhibitors; antisettling agents; anti-skinning agents; and antifoamingagents.
 3. A coating composition according to claim 1 in the form of apaint, wherein the active ingredient is present in an amount of from0.5% to 20% by weight of the composition.
 4. A coating compositionaccording to claim 1 in the form of a paint, wherein the activeingredient is present in an amount of from 1 to 10% by weight of thecomposition.
 5. A coating composition according to claim 1 in the formof an antifouling paint composition comprising up to 50% of the activeingredient by weight based on the total weight of the antifouling paintcomposition.
 6. A coating composition according to claim 1 in the formof an antifouling paint composition comprising from 5 to 25% of theactive ingredient by weight based on the total weight of the antifoulingpaint composition.
 7. A coating composition according to claim 1,wherein the compound of formula I is5,6-dihydro-3-(2-thienyl)-1,4,2-oxathiazine, 4-oxide or3-(4-chlorophenyl)-5,6-dihydro-1,4,2-oxathiazine, 4,4-dioxide.
 8. Acoating composition according to claim 6, wherein the compound offormula I is 5,6-dihydro-3-(2-thienyl)-1,4,2-oxathiazine, 4-oxide or3-(4-chlorophenyl)-5,6-dihydro-1,4,2-oxathiazine, 4,4-dioxide.